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PhEMD
Uncovering axes of variation among single-cell cancer specimens
ID:30489Uploader:BioTreasury
2022.01.19
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Abstract
While several tools have been developed to map axes of variation among individual cells, no analogous approaches exist for identifying axes of variation among multicellular biospecimens profiled at single-cell resolution. For this purpose, we developed 'phenotypic earth mover's distance' (PhEMD). PhEMD is a general method for embedding a 'manifold of manifolds', in which each datapoint in the higher-level manifold (of biospecimens) represents a collection of points that span a lower-level manifold (of cells). We apply PhEMD to a newly generated drug-screen dataset and demonstrate that PhEMD uncovers axes of cell subpopulational variation among a large set of perturbation conditions. Moreover, we show that PhEMD can be used to infer the phenotypes of biospecimens not directly profiled. Applied to clinical datasets, PhEMD generates a map of the patient-state space that highlights sources of patient-to-patient variation. PhEMD is scalable, compatible with leading batch-effect correction techniques and generalizable to multiple experimental designs.
Publication
Uncovering axes of variation among single-cell cancer specimens
William S. Chen,Nevena Zivanovic,David van Dijk,Guy Wolf,Bernd Bodenmiller,Smita KrishnaswamyNature Methods. 2020
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Single cell transcriptome
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